Tumor microsomal metabolism of the food toxicant, benzo(a)pyrene, in Apc Min mouse model of colon cancer

Abstract

The present study was conducted to investigate whether colon tumors were capable of metabolizing benzo(a)pyrene (BaP), and fluoranthene (FLA), two toxicants that belong to the polycyclic aromatic hydrocarbon family of compounds. Microsomes were isolated from the colon tumors of Apc( Min ) mice that received subchronic doses of 50 μg/kg BaP and incubated with either BaP or FLA (3 μM each) alone or in combination and appropriate control groups that received nothing. Subsequent to incubation, samples were extracted with ethyl acetate and analyzed for BaP and FLA metabolites by reverse-phase HPLC equipped with fluorescence detection. Microsomes from tumor tissues were found to metabolize BaP to a greater extent than those from the non-tumor tissues. The rate of BaP metabolism (picomoles of metabolite per minute per milligram of protein) was found to be more when microsomes from BaP-pretreated mice were exposed to BaP alone and FLA in combination with BaP, compared to controls. The microsomes from BaP-preexposed mice generated greater proportion of BaP 7,8-diol and BaP 3,6- and 6,12-diones compared to other experimental groups. Additionally, microsomes from BaP-pretreated mice produced greater proportion of FLA 2, 3-diol and 2, 3 D FLA when microsomes were incubated with FLA alone or a combination of BaP and FLA. Our studies revealed that the tumor microsomes were competent to metabolize BaP and FLA either singly or in combination. The biotransformation of BaP and FLA as a consequence of prior and simultaneous exposure to BaP may influence the growth of tumors. Our findings may have relevance to human long-term dietary intake of these toxicants and the consequent acceleration of the colon carcinogenesis process.